Tissues deprived of blood and oxygen undergo ischemic necrosis or infarction with possible irreversible organ damage. Once the flow of blood and oxygen is restored to the organ or tissue (reperfusion), the organ does not immediately return to the normal preischemic state. Reperfusion of coronary flow is necessary to resuscitate the ischemic or hypoxic tissue or organ. Timely reperfusion facilitates salvage of cells and decreases morbidity and mortality. Reperfusion of an ischemic area may result in a paradoxical dysfunction including marked endothelial cell dysfunction, which results in vasoconstriction, platelet and leukocyte activation, increased oxidant production, and increased fluid and protein extravasation.
Over the past two decades has witnessed several pharmacological interventions designed to limit reperfusion injury. Unfortunately, the success of some agents has been limited to experimental model of ischemia and reperfusion. The lack of consistent clinical benefit may be related to a variety of factors, including poor clinical trial design, inadequate pharmacokinentic/pharmacodynamic studies and the complexity of the human in vivo model.
There is a need in the art to distinguish therapeutic strategies for ischemia vs. reperfusion, and it is possible that a combination of agents is required to elicit the maximum clinical benefit.